dbSNP rs2733834: TYRP1:c.1409-67C>G (chr9-12708910-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000550.3(TYRP1):c.1409-67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,368,220 control chromosomes in the GnomAD database, including 260,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 21835 hom., cov: 34)

Exomes 𝑓: 0.60 ( 238359 hom. )

Consequence

TYRP1
NM_000550.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.34

Publications

5 publications found

Variant links:

Genes affected

TYRP1 (HGNC:12450): (tyrosinase related protein 1) This gene encodes a melanosomal enzyme that belongs to the tyrosinase family and plays an important role in the melanin biosynthetic pathway. Defects in this gene are the cause of rufous oculocutaneous albinism and oculocutaneous albinism type III. [provided by RefSeq, Mar 2009]

TYRP1 links:

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

LURAP1L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3 link	c.1409-67C>G		intron_variant	Intron 7 of 7	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1 link	n.317-8284G>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10 link	c.1409-67C>G		intron_variant	Intron 7 of 7	1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73877

AN:

151810

Hom.:

21826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.487

GnomAD4 exome

AF:

0.602

AC:

732752

AN:

1216292

Hom.:

238359

AF XY:

0.593

AC XY:

363013

AN XY:

612430

show subpopulations

African (AFR)

AF:

0.207

AC:

5724

AN:

27670

American (AMR)

AF:

0.440

AC:

16991

AN:

38642

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

13694

AN:

24252

East Asian (EAS)

AF:

0.00427

AC:

153

AN:

35820

South Asian (SAS)

AF:

0.268

AC:

20788

AN:

77620

European-Finnish (FIN)

AF:

0.714

AC:

33428

AN:

46832

Middle Eastern (MID)

AF:

0.437

AC:

2330

AN:

5332

European-Non Finnish (NFE)

AF:

0.673

AC:

611103

AN:

908242

Other (OTH)

AF:

0.550

AC:

28541

AN:

51882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

12876

25752

38629

51505

64381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14314

28628

42942

57256

71570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.487

AC:

73914

AN:

151928

Hom.:

21835

Cov.:

AF XY:

0.479

AC XY:

35577

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.223

AC:

9234

AN:

41482

American (AMR)

AF:

0.427

AC:

6498

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.550

AC:

1907

AN:

3468

East Asian (EAS)

AF:

0.0112

AC:

AN:

5156

South Asian (SAS)

AF:

0.233

AC:

1124

AN:

4822

European-Finnish (FIN)

AF:

0.718

AC:

7587

AN:

10568

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.676

AC:

45874

AN:

67880

Other (OTH)

AF:

0.482

AC:

1019

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1623

3246

4868

6491

8114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.490

Hom.:

1826

Bravo

AF:

0.458

Asia WGS

AF:

0.143

AC:

500

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.049

(source)

DANN

Benign

0.41

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over